To better understand factors which affect human development it is essential to appreciate the role of genetic factors in normal and abnormal developmental processes. It is our ogjective to study the biological and molecular nature of genetic regulatory elements which control the developmental expression of "structural" genes in specific tissues at certain developmental stages. The identification of autosomal genes, which can completely reverse the sex of the organism, demonstrates that these loci function as regulatory genes (i.e. switches) to control the expression of batteries of genes involved in sexually dimorphic functions. We propose to investigate the molecular aspects of sex determination in Drosophila by (1) identifying and characterizing the regulatory molecule encoded by the third chromosomal transformer (tra) gene and (2) studying the effect of the second chromosomal transformer-2 (tra-2) locus on the sexually dimorphic commitment of adult fat body cells to the expression of the yolk protein genes. To identify the tra+ gene roduct we propose to recover a recombinant DNA clone for the tra+ gene which can then be used to purify the tra gene transcript(s) as well as to monitor the expression of the wild-type tra+ gene. using a genomic clone which hybridizes near the tra+ locus and a series of newly generated deficiencies, we plan to "walk" and "jump" into the tra+ gene. Preliminary experiments with a recently recovered temperature sensitive allele of tra-2 indicate that the sexual phenotype of adult fata body cells can be changed by altering the activity of the tra-2 gene. In normal females, fat body cells produce yolk proteins in response to hormone while male fat body cells require 1000 fold exxxxcess of hormone for even low levels of induction. Since we find similar levels of hormone in both sexes, we will test the notion that the sexually dimorphic response of the male and female fat body cells is contarolled by altered levels of hormone receptors and that tra-2+ directly or indirectly controls these levels.